Tendinopathy, or degenerative tendons, affects millions of Americans in both occupational and athletic settings each year. Tendinopathy causes pain and discomfort, impairs work performance, and reduces quality of life. In spite of its high prevalence, current treatments of tendinopathy are not effective in restoring normal structure and function to degenerated tendons. In recent years, platelet-rich plasma (PRP) has been a popular treatment option for tendinopathy;however, whether PRP treatment is effective remains a huge controversy in orthopaedic/sports medicine. The overall objective of this project is to address this issue by defining the effects of clinically-relevant PRP treatments, along with tendon stem cells (TSCs) and engineered tendon matrix (ETM), on a validated rabbit tendinopathy model at the cellular, tissue, and functional levels. The specific aims of this project are: 1) to evaluate the effects of PRP treatment on the repair of tendinopathic tendons by PRP injection;2) to evaluate the effects of PRP treatment on the repair of tendinopathic tendons by implantation of PRP with TSCs;and 3) to evaluate the effects of adding ETM on the repair of tendinopathic tendons. This study is highly significant in light of the fact that PRP treatment is widely used in orthopaedic/sports medicine for tendinopathy treatment in the United States despite little available scientific data that support or refute its usages. This study is also highly innovative since a potent combination of natural healing growth factors (PRP), tendon-specific regenerative cells (TSCs), and tendon specific matrix (ETM) will be explored for the first time to enhance the repair of tendinopathic tendons. We anticipate that the findings of this study will lead to the application of this combination therapy clinically to effectively repair or possibly regenerate tendinopathic tendons, thus benefiting millions of tendinopathic patients in the United States alone. PUBLIC HEALTH RELEVANCE: This project aims to enhance repair of degenerative tendons (tendinopathy) using platelet-rich plasma (PRP), regenerative tendon-specific stem cells, and engineered tendon matrix. The results of this study will impact orthopaedic/sports medicine practice by providing much awaited scientific data on PRP treatment of tendinopathy.